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Cancer Bioinformatics Infrastructure Objects (caBIO)
Architecting the Future of Genomics
http://ncicb.nci.nih.gov
Himanso Sahni & Scott GustafsonDecember 7, 2001Science Applications International Corporation (SAIC)
caBIO Team
caBIO was developed as “open source” technology by the National Cancer Institute Center for Bioinformatics
(NCICB)
Software developers teamed with scientists from the NCICB Cancer Genome
Anatomy Project (CGAP) to define caBIO requirements and use cases, and
model the genomics domain
Purpose
“To provide an overview of caBIO, its current role in
genomics, and future transitions towards intelligent genomics”
The Genomic Past
Little or no data integration Lack of standards Little or no software code re-use Duplication of efforts Duplication of data Lack of common vocabulary Maintenance nightmares
The Genomic Challenge
Code Re-Use
INTELLIGENCE!http://ncicb.nci.nih.gov
Data Integration
Standards
Increased ProductivityCommon Vocabulary
Ease of Maintenance
Normalized Data
caBIO Overview
caBIO is a standards based set of genomic components
caBIO objects simulate the behavior of actual genomic components such as genes, chromosomes, sequences, libraries, clones, ontologies, etc.
caBIO objects provide access to a variety of genomic data sources including GenBank, Unigene, LocusLink, Homologene, Ensemble, GoldenPath, and NCICB’s CGAP (Cancer Genome Anatomy Project) data repositories
caBIO is “open source”
Development Process
Iterative Approach– An iterative software
design and development approach leveraging concepts from RUP and XP was used
– Initial Vision and High Level Analysis form the overall goals of the project
– Iterative functional design and implementation processes allows for rapid and segmented development of the application
Development Process
High Level Use Cases– Initial high level Use
Cases were developed for gene components
– Additional high level Use Cases were added as additional functional areas are mapped (e.g. pathways, therapies, microarray objects, mouse models)
– Detailed Use Cases are derived from working with domain experts in requirements gathering.
Development Process
Detailed Use CasesDetailed Use Cases• Detailed Use Cases Detailed Use Cases
were derived from were derived from teaming with domain teaming with domain experts during experts during requirements gatheringrequirements gathering
• Detailed Use Cases Detailed Use Cases includeinclude
• Characteristic Characteristic InformationInformation
• Main Success Main Success ScenarioScenario
• ExtensionsExtensions• Related InformationRelated Information
Development Process
Class Diagrams– Class Diagrams
were developed using the Unified Modeling Language (UML)
– The class diagram is continually updated as new objects and relationships are defined
Development Process
ObjectsObjects• Each object consists of Each object consists of
many attributes, many attributes, operations, and operations, and associationsassociations
• For example a gene For example a gene object has many object has many attributes such as attributes such as symbols and keywords. symbols and keywords. A gene also has A gene also has operations including operations including getName and getName and getSequnces, and getSequnces, and associations which associations which indicate that a gene indicate that a gene “has” sequences and “has” sequences and “has a ” location “has a ” location
Development Process
Sequence Diagrams– Additional
methods are discovered as the objects are further explored modeling the use cases
Development Process
Object Development– Java Code is
written to implement the Object Model
– Documentation (API) is built from the Java Code
Development Process
Application Development– Applications
leveraging caBIO can be developed using multiple programming languages
Development Process
Example Application– caBIO was used to add
intelligence to BioCarta pathways
• Gene, pathway, and expression objects were used
– Users can select a pathway, and view pathway components that are mutated or expressed
– Users can drill down to detailed gene information
– http://cmap-prot.nci.nih.gov
Architecture
External Java Apps
Clients Presentation Layer Object Layer Data Sources
Browsers
Other Apps
HTML/HTTP
XML/HTTP
RDF
Internal Java Apps
Web Server
Servlet Container
JSPs
Servlets
UI Bean
XML Builder
XSLT Engine
SOAP Engine
XML Docs
DTDsXSL
Style Sheet
RMI
URLs
Flat Files
DatabasesDatabases
Genes Chromosomes
Libraries
Tissues Clusters
Object Managers
JDBC
HTTP
FTP
Agents
SOAP
Data Access Objects
Sequences
Diseases
Other
Domain Objects
Architecture
The core infrastructure exhibits an n-tiered architecture with client interfaces, server components, back-end objects and data sources
Clients (browsers, applications) can receive information (HTML and XML) from back-end objects over HTTP– Client applications can also communicate with back-end objects via
Java RMI (Java applications)– Non-Java based applications will communicate via SOAP
Server components communicate with back-end objects via Java RMI
Back-end objects communicate directly with data sources (database, URLs, flat files)
A UDDI registry will be configured to advertise services– RDF is currently used to advertise services to crawlers and agents
Architecture
Client Technology • Industry Standard Web Browsers - Netscape 4+ and IE 4+• Java Applications – Applications that implement the Java programming
language, an object-oriented language which provides portability and many other features
• Non-Java Applications - Applications usually written in Perl, C, etc.– Non-Java applications use SOAP clients to interface with caBIO
» SOAP::Lite for Perl – A collection of Perl modules which provides a simple and lightweight interface to the Simple Object Access Protocol (SOAP)
• Agents - Software programs that perform a function for a user in a trusted fashion, can learn or be taught its function, and can perform actions for the user without permission
• RDF – The Resource Description Framework is a foundation that advertises Web services via the Web. RDF is used to describe the content and services available at a particular Web site. (passive)
• UDDI – Universal Description, Discovery and Integration is a foundation to enable businesses to discover and transact business with each other using preferred applications (active)
Architecture
Presentation Layer Technology– Jakarta Tomcat - Servlet+JSP Engine which is a subproject of
the Jakarta Project– JSPs - Java Server Pages are web pages with Java embedded
in the HTML to incorporate dynamic content in the page– Java Servlets – Server-side Java programs that web servers can
run to generate content in response to client requests– Java Beans – Reusable software components that work with
Java– XML – The Extensible Markup Language is a universal format for
structured data on the Web• XSL/XSLT – The Extensible Stylesheet Language is a language for
expressing stylesheets. XSL Transformations (XSLT) is a language for transforming XML documents
• XLink – The XML Linking Language allows elements to be inserted into XML documents in order to create and describe links between resources
• DOM – The Document Object Model is a platform and language independent interface that allows programs to dynamically access content, structure, and document style
Architecture
Presentation Layer Technology(cont.)– SOAP – The Simple Object Access Protocol is a
lightweight XML based protocol for the exchange of information in a decentralized, distributed environment. It consists of an envelope that describes the message and a framework for message transport
• Apache SOAP – An implementation of the W3C SOAP specification. The Apache SOAP provides a server-side infrastructure for deploying, managing, and running SOAP enabled services.
Presentation Layer– The Mediator Servlet manages
the user session, forwards requests to the JSP, and returns HTML
– JSPs forward requests to the UI Bean, and returns XML or HTML to the client
– The UI Bean receives the a Domain Object and converts the object to XML or HTML
– The DOM Writer performs the Conversion to XML while the Conversion Servlet represents the Domain Object as a Document Object (DOM)
• The conversion is performed by calling the Domain Objects toXML() method
Architecture
XML Builder
HTML/HTTP
XML/HTTP
RDF
RMI
SOAP
Mediator Servlet
ConversionServlet
JSPs
DOM Writer
UI Bean Manager Proxies
Domain Objects
Architecture
Object Layer Technology– Java Applications/Objects – Applications/Objects that implement
the Java programming language, an object-oriented language which provides portability and many other features
– Java RMI – Remote Method Invocation is distributed computing in Java. It is a simple technology for object communication that allows remote objects to act as local Java objects
– JDBC – Java Database Connectivity is a Java API for executing SQL statements and connecting to databases
– SOAP – Simple Object Access Protocol extends object interoperability to other programming languages (Perl, Python, C++)
– DAS – The Distributed Annotation System is an emergent system for retrieving genomic annotations from a variety of data sources (GoldenPath, Ensembl)
Object Managers
Object Layer– Object Managers are
created to implement complex scientific concepts
– The Role Model object verifies user permissions to the data if applicable
– The Remote Manager interface abstracts the RMI layer
• Allows RMI to be easily replaced by EJB or other communication venues
– Domain Objects are serialized and XML enabled
Architecture
RMI
Role Model
Remote Interface Manager
GeneManager
SequenceManager
LibraryManager
Other Managers
Data Access Objects
Domain Objects
Data Access Objects– Provides the object
relational mapping
– Database independent persistence
– Allows for the introduction of new data sources
– Abstracts persistence details from the domain objects
– Allows for federated database topology
LibraryPersistence
GenePersistence
TissuePersistence
SequencePersistence
Other
ClonePersistence
ProteinPersistence
Architecture
Data Sources
URLs
Flat Files
DatabasesDatabases
JDBC
HTTP
FTP
Data Access Objects
Data Sources
CGAP (NCI Cancer Genome Anatomy Project)– Provides gene expression profiles of normal, pre-
cancer, and cancer cells GenBank (NCBI)
– Sequence submission software Unigene (NCBI)
– Partitions sequences into unique gene-oriented clusters
LocusLink (NCBI)– Provides an interface to curated sequence and
descriptive info about genetic loci
Data Sources
Homologene (NCBI)– Provides curated orthologs and homologs
for UniGene and LocusLink genes GoldenPath (UCSC)
– Contains a working draft of the human genome
Usage
Java developers use the caBIO jar file for immediate access to genomic object attributes and methods– caBIO objects can easily be extended to support customized
objects Non-Java and Java developers can use SOAP to
access genomic object attributes and methods over HTTP
Developers can obtain detailed descriptions of available services via the RDF site– URIs of desired services can be obtained via RDF
Developers can host a caBIO server or leverage the existing NCICB caBIO server
Benefits
Provides an abstraction layer that allows developers to access genomic information using a standardized tool set without concerns for implementation details
Permits access to allow developers to obtain the information they need from a variety of data sources without data management
Manages the display of large volumes of data to assist in load balancing
Provides an effective mechanism for comparing similar objects that rely on diverse data sources
Facilitates information sharing without managing linkages between multiple data sources
Future
The Semantic Web– Concept
• “The Semantic Web is an extension of the current web in which information is given well-defined meaning, better enabling computers and people to work in cooperation." -- Tim Berners-Lee, James Hendler, Ora Lassila (W3C)
– Implementation• Agent Based Technology may be used to create programs that
implement semantic web concepts
Natural Language Processing (NLP) – NLP involves understanding natural language and extracting
information – NLP can be used as a tool to help automate tasks, refine
searches and improve genomic algorithms